Pirtobrutinib, a novel BTK inhibitors for chronic lymphocytic leukemia
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by An Duc Thien Le |
Posted on August 7th, 2023
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BTK inhibitors such as ibrutinib, and zanubrutinib are safe and effective treatments for patients with chronic lymphocytic leukemia. However, resistance can be acquired in the form of C481 mutation. Thus, venetoclax can be used for these cases; however, its usage required careful dose-escalation in an inpatient setting. Recently, Pirtobrutinib, a new BTK inhibitor, has been assessed to see if it can be utilized to treat chronic lymphocytic leukemia, and the result from the investigation has been published onto the New England Journal of Medicine.
Pirtobrutinib had previously been approved to treat mantle-cell lymphoma by the Food and Drug Administration. The agent is different from other approved BTK inhibitors, because it is less selective so it can bind to both wild-type and C481-mutant BTK. The clinical trial included a total of 317 patients who had been diagnosed with chronic lymphocytic leukemia, and the phase 1 study was performed to determine the best dose of pirtobrutinib to be 200 mg. Subsequently in the phase 2 trial, the patients were given 200 mg of pirtobrutinib once daily in a 28-day cycle. CT scan and bone marrow analysis were performed in conjunction to the clinical symptoms monitoring to assess the effect of the medication. After a median treatment duration of 16.5 months, the researchers concluded that pirtobrutinib help reduce the amount of cancer cells in 73.3% of the patients. The progression-free survival duration of these patients was 19.6 months. Safety assessment showed that infections occur in 71% of the patients; bleeding in 42.6%; neutropenia in 32.5%. Only 9 patients discontinue treatment due to side effects. Currently, there are ongoing phase 3 clinical trials being conducted to further understand the clinical efficacy and safety profile of pirtobrutinib in comparison to placebo and other treatments.
Pirtobrutinib had previously been approved to treat mantle-cell lymphoma by the Food and Drug Administration. The agent is different from other approved BTK inhibitors, because it is less selective so it can bind to both wild-type and C481-mutant BTK. The clinical trial included a total of 317 patients who had been diagnosed with chronic lymphocytic leukemia, and the phase 1 study was performed to determine the best dose of pirtobrutinib to be 200 mg. Subsequently in the phase 2 trial, the patients were given 200 mg of pirtobrutinib once daily in a 28-day cycle. CT scan and bone marrow analysis were performed in conjunction to the clinical symptoms monitoring to assess the effect of the medication. After a median treatment duration of 16.5 months, the researchers concluded that pirtobrutinib help reduce the amount of cancer cells in 73.3% of the patients. The progression-free survival duration of these patients was 19.6 months. Safety assessment showed that infections occur in 71% of the patients; bleeding in 42.6%; neutropenia in 32.5%. Only 9 patients discontinue treatment due to side effects. Currently, there are ongoing phase 3 clinical trials being conducted to further understand the clinical efficacy and safety profile of pirtobrutinib in comparison to placebo and other treatments.